Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Risk Factors in Different Subsets of Rheumatoid Arthritis.

Lundberg3,  Karin, Bengtsson1,  Camilla, Israelsson4,  Lena, Pollak-Dorocic4,  Iskra, Padyukov4,  Leonid, Alfredsson1,  Lars, Malmstrom4,  Vivianne

Institute for Environmental Medicine, Karolinska Institutet
Karolinska University Hospital, Stockholm, Sweden
Reumatology Unit, Karolinska Institutet, Stockholm, Sweden
Reumatology Unit, Karolinska Institutet

Background:

Risk factors for rheumatoid arthritis (RA), such as HLA-DRB1'shared epitope' (SE) alleles, PTPN22 and cigarette smoking, associate with anti-CCP positive disease. By subdividing CCP positive patients based on reactivity to CEP-1, the immunodominant B cell epitope on citrullinated alpha-enolase, we have previously shown that SE, PTPN22 and smoking mainly constitute risk factors for CEP-1 positive, rather than CCP positive RA. Here, we investigate 5 RA subsets, grouped based on reactivity to CCP, CEP-1 and a citrullinated vimentin peptide (CitVim), representing another anti-citrullinated protein/peptide antibody (ACPA)-specificity.

Methods:

Antibodies were analysed in serum from 1027 RA patients from the Epidemiological Investigation of RA (EIRA), a Swedish population-based case-control study. An ELISA was set up for detection of anti-CitVim antibodies, using a biotinylated CitVim peptide (amino acid 60–75). One hundred and fifty healthy controls were used to determine the 95th percentile cut-off. A positive and a negative control and a standard of pooled anti-CitVim positive serum were included on each plate. Anti-CCP was measured using the Immunoscan CCPlus kit (Euro-Diagnostica) and anti-CEP-1, using an in-house ELISA previously described (Mahdi et al, Nature Genetics, 2009). Different RA subsets were compared with regard to risk factors by calculating odds ratios (OR) with 95% confidence interval by means of logistic regression.

Results:

Patients were divided into 5 subsets: CEP-1+/CitVim+ (41%); CEP-1+/CitVim- (15%); CEP-1-/CitVim+ (11%) (the majority of patients in these subsets were anti-CCP positive and not divided further based on CCP status); CEP-1-/CitVim-/CCP+ (18%) and CEP-1-/CitVim-/CCP- (15%). SE, PTPN22 and smoking each showed strongest association in the CEP-1+/CitVim+ subset, intermediate association in the single positive subsets and low association in the ACPA negative subset. The combined effect of risk factors showed a similar pattern, with an OR of 52 in the double positive subset, 16 in the CEP-1 single positive, 5 in the CitVim single positive, 6 in the CCP single positive, and 2 in the triple negative. Additionally, antibody levels were higher in CEP-1+/CitVim+ patients compared to single positive patients.

Conclusion:

Our data show that the anti-CEP-1 and the anti-CitVim antibody response only partly overlap, and that SE, PTPN22 and smoking predispose to the development of ACPA with multiple reactivities, rather than one single specificity. Interestingly, the CEP-1-/CitVim-/CCP+ subset still showed a strong association with SE (OR: 12), suggesting that other ACPA fine-specificities, for example citrullinated fibrinogen or collagen type II, could be found in this subset.

To cite this abstract, please use the following information:
Lundberg, Karin, Bengtsson, Camilla, Israelsson, Lena, Pollak-Dorocic, Iskra, Padyukov, Leonid, Alfredsson, Lars, et al; Risk Factors in Different Subsets of Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2118
DOI: 10.1002/art.29882

Abstract Supplement

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